Perrault syndrome type 3 caused by diverse molecular defects in CLPP

Scientific Reports
Erica J BrodieDavid A Dougan

Abstract

The maintenance of mitochondrial protein homeostasis (proteostasis) is crucial for correct cellular function. Recently, several mutations in the mitochondrial protease CLPP have been identified in patients with Perrault syndrome 3 (PRLTS3). These mutations can be arranged into two groups, those that cluster near the docking site (hydrophobic pocket, Hp) for the cognate unfoldase CLPX (i.e. T145P and C147S) and those that are adjacent to the active site of the peptidase (i.e. Y229D). Here we report the biochemical consequence of mutations in both regions. The Y229D mutant not only inhibited CLPP-peptidase activity, but unexpectedly also prevented CLPX-docking, thereby blocking the turnover of both peptide and protein substrates. In contrast, Hp mutations cause a range of biochemical defects in CLPP, from no observable change to CLPP activity for the C147S mutant, to dramatic disruption of most activities for the "gain-of-function" mutant T145P - including loss of oligomeric assembly and enhanced peptidase activity.

References

Mar 30, 2002·The Journal of Biological Chemistry·Sung Gyun KangMichael R Maurizi
Apr 5, 2002·Molecular Cell·David A DouganBernd Bukau
Aug 23, 2002·Biochimica Et Biophysica Acta·Oleksandr GakhGrazia Isaya
Aug 29, 2002·The Journal of Biological Chemistry·Amelia J JohnstonMichael T Ryan
Apr 6, 2004·Nature Structural & Molecular Biology·Shilpa A JoshiRobert T Sauer
Apr 21, 2004·Protein Science : a Publication of the Protein Society·Ann-Maree CatanzaritiRohan T Baker
Aug 12, 2004·Nucleic Acids Research·Lei ZhengJean-Louis Reymond
Nov 4, 2004·Journal of Structural Biology·Sung Gyun KangBijan Ahvazi
Aug 24, 2005·The Journal of Biological Chemistry·Sung Gyun KangMichael R Maurizi
Apr 21, 2007·Methods in Cell Biology·Diana StojanovskiNils Wiedemann
Feb 5, 2008·American Journal of Medical Genetics. Part a·Sandrine MarlinFrançoise Denoyelle
Apr 27, 2010·Journal of Molecular Biology·Mary E LeeRobert T Sauer
Apr 6, 2011·Proceedings of the National Academy of Sciences of the United States of America·Sarah B PierceMary-Claire King
Nov 1, 2011·Journal of Neurology·Emma M JenkinsonWilliam G Newman
Dec 3, 2011·BMC Biochemistry·Nadia BenaroudjMiguel Ortiz-Lombardia
Jun 20, 2012·Journal of Structural Biology·Bradley R LowthDavid A Dougan
Apr 2, 2013·American Journal of Human Genetics·Emma M JenkinsonWilliam G Newman
Jan 15, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ayenachew Bezawork-GeletaKaye N Truscott
Nov 26, 2015·ACS Chemical Biology·Malte GerschStephan A Sieber
Mar 13, 2016·Clinical Genetics·L A M DemainW G Newman
Apr 19, 2016·Journal of Clinical Research in Pediatric Endocrinology·Fatma DursunHeves Kırmızıbekmez
May 14, 2016·ACS Chemical Biology·Tengfeng NiCai-Guang Yang
Nov 1, 2016·The EMBO Journal·Karolina SzczepanowskaAleksandra Trifunovic
Dec 3, 2016·Frontiers in Neurology·Tom E J TheunissenHubert J M Smeets
Apr 28, 2017·Human Molecular Genetics·Iliana A ChatzispyrouAstrid S Plomp

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Citations

Jan 14, 2020·Annual Review of Biophysics·Linhao RuanRong Li
Aug 9, 2019·Endocrinology·Dov TiosanoDavid A Buchner
May 20, 2020·BMC Medical Genetics·Maria Teresa Carminho-RodriguesAriane Paoloni-Giacobino
Oct 11, 2020·Cell Death & Disease·Kazem NouriAaron D Schimmer
Dec 15, 2020·FEBS Letters·Alberto FerrariAntoni Barrientos
Jan 17, 2021·FEBS Letters·Maria Gomez-Fabra Gala, Friederike-Nora Vögtle
Oct 24, 2020·Nature Reviews. Molecular Cell Biology·Jiyao SongThomas Becker
Mar 19, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sylvia Torres-OdioA Phillip West
Jun 11, 2021·Frontiers in Molecular Biosciences·Heike Brötz-Oesterhelt, Andreas Vorbach
Jul 3, 2021·International Journal of Molecular Sciences·Antonella CormioClara Musicco
Aug 8, 2021·International Journal of Molecular Sciences·Henrieta HavalováNina Kunová
May 23, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Denise DittmarUlf Gerth

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Methods Mentioned

BETA
Gel Filtration
immunoprecipitation
Protein sequencing
co-immunoprecipitation
size exclusion chromatography
electrophoresis
co-IP
coIP

Software Mentioned

Chromlab
ImageQuant

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